Registry and biobank establishment of inflammatory bowel disease suspected to primary immunodeficiency diseases for the first time in Iran and as a partner of international campaign

SLC26A3 [downregulated in adenoma (DRA)] plays a key role in mammalian intestinal NaCl absorption, in that it mediates apical membrane Cl−/[Formula: see text] exchange. DRA function and expression are significantly decreased in diarrhea associated with inflammatory bowel disease. DRA is also considered to be a marker of cellular differentiation and is predominantly expressed in differentiated epithelial cells. Caudal-type homeobox protein-2 (CDX2) is known to regulate genes involved in intestinal epithelial differentiation and proliferation. Reduced expression of both DRA and CDX2 in intestinal inflammation prompted us to study whether the DRA gene is directly regulated by CDX2. Our initial studies utilizing CDX2 knockout (CDX2fV/fV;Cre+) mice showed a marked reduction in DRA mRNA and protein levels in proximal and distal colon. In silico analysis of the DRA promoter showed two consensus sites for CDX2 binding. Therefore, we utilized Caco-2 cells as an in vitro model to examine if DRA is a direct target of CDX2 regulation. siRNA-mediated silencing of CDX2 in Caco-2 cells resulted in a marked (~50%) decrease in DRA mRNA and protein levels, whereas ectopic overexpression of CDX2 upregulated DRA expression and also stimulated DRA promoter activity, suggesting transcriptional regulation. Electrophoretic mobility shift and chromatin immunoprecipitation assays demonstrated direct binding of CDX2 to one of the two putative CDX2 binding sites in the DRA promoter (+645/+663). In summary, our studies, for the first time, demonstrate transcriptional regulation of DRA expression by CDX2, implying that reduced expression of DRA in inflammatory bowel disease-associated diarrhea may, in part, be due to downregulation of CDX2 in the inflamed mucosa. NEW & NOTEWORTHY SLC26A3 [downregulated in adenoma (DRA)] mediates intestinal luminal NaCl absorption and is downregulated in inflammatory bowel disease-associated diarrhea. Since both DRA and caudal-type homeobox protein-2 (CDX2) are reduced in intestinal inflammation and the DRA promoter harbors CDX2 binding sites, we examined whether the DRA gene is regulated by CDX2. Our studies, for the first time, demonstrate transcriptional regulation of DRA expression by CDX2 via direct binding to the DRA promoter, suggesting that reduced expression of DRA in inflammatory bowel disease-associated diarrhea could, in part, be attributed to downregulation of CDX2.

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Efficacy of Anti-TNF Therapy for the Treatment of Patients with Moderate-to-Severe Inflammatory Bowel Disease; a First Iranian Report

Middle East Journal of Digestive Diseases ◽

10.15171/mejdd.2020.158 ◽

2019 ◽

Vol 12 (1) ◽

pp. 12-18

Author(s):

Samaneh Mohagheghi Darehranj ◽

Sudabeh Alatab ◽

Homayoon Vahedi ◽

Anahita Sadeghi ◽

Alireza Sima ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Adverse Events ◽

Bowel Disease ◽

National Level ◽

Complete Response ◽

Drug Discontinuation ◽

Serious Adverse Events ◽

Inflammatory Bowel ◽

One Year ◽

First Time

BACKGROUND The anti-TNF drugs are shown to be highly effective in treatment of patients with moderate-tosevere inflammatory bowel disease (IBD). Here, we aimed to assess the efficacy and safety of antiTNF therapy at the national level. METHODS IBD patients aged 15 > years who received Infliximab and/or CinnoRA® between 2013 to July 2018 were identified. The data extracted from medical dossier and telephonic interview. The efficacy of therapy was defined as time to drug discontinuation or need for IBD-related surgery. The safety was assessed based on patient’s reported adverse events. RESULTS We included 315 patients. The mean age of patients was 37.2 years and 62.2% of them developed the disease before age 30 years. Involvement of masculoskeletal system was reported in 7.3% of patients. Partial and complete response to Anti-TNF therapy was seen in 67% of patients. About 16% of patients did not respond to induction therapy and 16.9% of patients lost their response to Anti-TNF during one year. No serious adverse events, serious opportunistic infection, tuberculosis and malignancies reported by patients. Two patients reported pneumonia. CONCLUSION This study for the first time in our country, provides the evidences for efficacy of anti-TNF therapy in moderate to severe IBD patients.

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Features of very early-onset inflammatory bowel disease: the experience of the Federal Pediatric Center

Voprosy detskoj dietologii ◽

10.20953/1727-5784-2021-3-5-13 ◽

2021 ◽

Vol 19 (3) ◽

pp. 5-13

Author(s):

P.V. Shumilov ◽

◽

A.E. Shchigoleva ◽

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Primary Immunodeficiency ◽

Bowel Disease ◽

Early Onset ◽

Activity Index ◽

Response To Therapy ◽

Inflammatory Bowel

Objective. To clarify the incidence of monogenic IBD-like diseases and the features of clinical course and response to therapy of major types of inflammatory bowel diseases (IBD) among children under the age of 6 with manifestation of the disease. Patients and methods. The study included 135 children under the age of 6 with manifestation of IBD; in the comparison group, there were 128 children after the age of 6 with manifestation of IBD (97 children with ulcerative colitis (UC) and 31 children with Crohn’s disease (CD)) who were observed for at least 1 year. All children underwent a standard examination, including calprotectin and antineutrophil antibodies testing, determination of activity by the Pediatric Ulcerative Colitis Activity Index (PUCAI) or the Pediatric Crohn’s Disease Activity Index (PCDAI), depending on the nosology. Children with the onset of IBD under 6 years of age underwent a genetic testing using Primary Immunodeficiency Panel by next-generation sequencing. All children were analyzed for efficacy of therapy during catamnestic observation. Results. It was revealed that in the study group the incidence of monogenic IBD-like diseases was 6.7%, of UC – 71.1%, of CD – 22.2%. Major types of IBD with very early onset differed little in their clinical, endoscopic and laboratory features from the forms with manifestation at an older age. In most cases, both CD (57%) and UC (71%) were characterized by low activity. Very earlyonset CD was characterized by isolated localization of the colon (53%, p = 0.037) and a non-stenotic and non-penetrating behaviour of the disease (60% of cases). The leading clinical symptoms were diarrhea (67%) and blood in the stool (63%, p = 0.04). Very early-onset UC was characterized by total lesion of the colon (84%, p = 0.001) and the development of anemia (48%, p = 0.01). Among children with very early-onset UC, the percentage of glucocorticosteroid-dependence and glucocorticosteroid-resistance was high, but anti-TNFα therapy was prescribed late. Conclusion. It is advisable to observe children with very early-onset IBD in federal multidisciplinary clinics, where there is experience in managing patients with this pathology. Key words: inflammatory bowel disease, very early onset, Crohn’s disease, ulcerative colitis, primary immunodeficiency, treatment, children

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